Nasal production of IL-26 involving T cells in smokers with and without chronic obstructive pulmonary disease

Abstract

Background: Novel specific therapy in chronic obstructive pulmonary disease (COPD) will require accessible targets for endotyping to identify responsive patients. It is therefore of interest that IL-26 in the bronchoalveolar space is enhanced and associates with bronchoalveolar pathology among long-term smokers (LTS) with and without COPD.

Objective: We determined whether IL-26 in the nasal cavity can be produced by T cells and associates with bronchoalveolar pathology and clinical symptoms in LTS with and without COPD.

Methods: We characterized LTS with and without COPD plus healthy nonsmokers by radiology, spirometry, modified Medical Research Council scale, and St George Respiratory Questionnaire. We determined extracellular IL-26 concentrations (via ELISA) in nasal (NAL) and bronchoalveolar lavage (BAL) samples, BAL neutrophil counts, and NAL IL-26⁺ T-cell expression (via flow cytometry).

Results: The NAL IL-26 concentrations were higher in LTS with COPD than in healthy nonsmokers. These enhanced IL-26 concentrations displayed a positive correlation with forced expiratory volume in 1 second/forced vital capacity ratio. The IL-26 protein was expressed in CD4⁺ and CD8⁺ T cells, but only a small portion of these cells coexpressed IL-15, IL-17A, or IL-22 in LTS with COPD. In this group, IL-26⁺ CD3⁺ T cells displayed a negative correlation with forced expiratory volume in 1 second, as did with extracellular NAL IL-26 concentrations. The relative mean fluorescence intensity for CD8⁺ T cells displayed a negative correlation with modified Medical Research Council and St George Respiratory Questionnaire score.

Conclusion: In the nasal cavity, IL-26 can be produced by local T cells. This IL-26 reflects bronchoalveolar pathology and clinical symptoms, thereby constituting an accessible target with potential for clinically relevant endotyping in COPD.

Keywords: Bronchoalveolar lavage; COPD; IL-26; bronchoalveolar pathology; lung function; nasal cavity; nasal lavage.